Field of Technology
The disclosure relates to both a device and a method for identifying solid and liquid materials using near-infrared transmission spectroscopy combined with multivariate calibration methods for analyzing the near-infrared spectra. One important application of the device and method is the detection of counterfeit drug tablets and capsules.
Background
Six optical spectroscopic devices/methods that have been previously developed include: 1) light-emitting diode (LED) based spectrometer analyzers operating in the short wavelength 600-1100 nm region of the near-infrared range that use modulated LEDs; 2) Fourier-transform near-infrared spectrometers; 3) diffraction grating based near-infrared spectrometer systems (desktop size instruments that do not employ LEDs to measure the spectrum) that operate in the 800-2500 nm range (and also portable spectrometers operating in the same near-infrared range); 4) tunable acousto-optic based near-infrared spectrometers; 5) Hadamard transform based near-infrared spectrometers; and 6) laser-Raman spectrometers. The existing LED near-infrared spectrometers have been used for quantitative analysis of agricultural, fuel, and paper products. Existing Fourier-transform and single detector diffraction grating near-infrared spectrometers have been used for analysis of pharmaceutical tablets including analysis for identification of counterfeit drugs as well as other types of material identification and analysis. Existing tunable acousto-optic filter based near-infrared spectrometers could be used for identification of counterfeit drugs. An existing Hadamard transform spectrometer has been used for identification of counterfeit drugs and identification of polymers and other materials. The laser-Raman spectrometers, which have been used for drug, polymer, and general chemical identification, are usually based on a diffraction grating spectrometer with a Si-CCD of InGaAs array detection with single wavelength laser excitation at 785 or 1064 nm. Fourier-transform based laser Raman spectrometers are also available and have been used for similar applications.
The LED spectrometers described in the literature include both handheld and desktop size devices that have been used for analyzing gasoline and other petroleum fuels to measure parameters such as octane rating, and also to analyze grain and meat samples for water, fat and protein content, and also paper samples for water. In addition to operating in the 600-1050 nm wavelength range, the existing LED spectrometers use 31 or 32 LED light sources, and a wavelength filtering means consisting of either narrow bandpass interference filters associated with each LED and/or with narrow bandpass filtering of the light reaching the sample from each LED by transmission through a slit and reflection off of a diffraction grating. The existing commercial LED spectrometers employ Si photodiode detectors. Compared to the other optical spectroscopic devices, the existing LED based spectrometers have much lower spectral resolution with only 32 wavelength points compared to 512 or more points for the other technologies.
The identification of chemical components in pharmaceutical tablets and capsules and identification of counterfeit tablets and capsules has been reported using near-infrared transmission spectroscopy, where light is transmitted all the way through the tablet or capsule, with larger desktop size Fourier-transform near-infrared spectrometers and desktop size diffraction grating based near-infrared spectrometers that employ single element photodiode detectors. These spectrometers all employ a tungsten-halogen light source emitting over a wide wavelength range and measure transmission spectra by filtering the light either with a diffraction grating based monochromator, or a Michelson interferometer. These desktop instruments have a disadvantage in both high cost (about $50,000) and large size/weight relative to the new system described herein, which would greatly limit their application in testing for counterfeit drugs at drug distribution centers in developing countries. The identification of counterfeit drug tablets and capsules has also been reported with commercially available portable spectrometers including near-infrared diffraction grating array detector, near-infrared Hadamard transform, and laser-Raman spectrometers which all operate only in a reflection sampling mode. These latter spectrometers have a high cost of about $30,000-$45,000. Sampling by reflection is much less desirable than sampling by transmission because transmission sampling measures the average composition of the major portion of the entire volume of a drug tablet or capsule, while reflection sampling only sees an outer portion of the tablet/capsule that is less than 1 mm deep, and just on one side. Drug tablets are known to have substantial inhomogeneity in the distribution of active ingredients over distances on the order of 1 mm. In cases of tablets with coatings, the coatings must be removed by abrasion or cutting before analysis using surface reflection sampling. The tunable acousto-optic spectrometers have not been used for counterfeit drug identification and also have a high cost greater than $30,000.
A commercially available wet chemical test kit has been developed by the World Health Organization for testing the authenticity of drugs. To analyze tablets or capsules with this wet chemical test kit it is necessary to dissolve the sample tablet/capsule in water and then add one or more chemical reagents or then to perform a thin layer chromatography step, which are all time consuming and destructive processes (taking over 10 minutes per measurement) which consumes chemical reagents. This kit has a price of about $5,000. and a reagent kit replacement cost of $1,500 (good for 1,000 tests).
The device disclosed herein can be comparably priced to this wet chemical test kit, but has major advantages including an analysis time of about 10 to 15 seconds, and no required reagents or sample preparation.
It is also not obvious, based on existing literature, that a low-cost miniature diffraction grating, array detector near-infrared (NIR) spectrometer that operates over the 650-1100 nm wavelength range (with signal/noise of about 3000:1, and spectral resolution of 1.5 nm, with a measurement time of 15 seconds or less) would have sufficient signal/noise and detection sensitivity to measure transmission spectra through drug tablet and capsule samples and other materials (materials with an optical attenuation in the range of ×100 to ×10,000) with sufficient quality to determine the authenticity of these tablet and capsule samples or to identify the materials. Typical drug tablet and capsule samples have a high level of optical attenuation for light transmitted through the entire tablet/capsule thickness that is on the order of 104. Previously, only desktop sized Fourier Transform NIR spectrometers and scanned diffraction grating NIR spectrometers with much higher price and with much higher signal/noise than the miniature diffraction grating/Si-array detector spectrometers) have been used for NIR spectroscopic drug tablet/capsule authentication using transmission sampling. These larger and more expensive spectrometers employ single element InGaAs detectors (as opposed to Si based linear array detectors) that have much higher signal/noise on the order of 20,000 to 50,000:1 relative to the miniature array detector spectrometers which have signal/noise rations on the order of 500:1 to 3,000:1. Also, the desktop single detector NIR spectrometers operate over a wider 800-2500 nm NIR spectral range as opposed to the 650-1100 nm range of the low-cost miniature diffraction grating spectrometers with Si based array detectors. For less attenuating samples such as nonscattering (clear) liquid samples measured by transmission and powder samples measured by diffuse reflectance, diffraction grating Si-array detector spectrometers have been used for materials identification, but this has not been done with the ultra-miniature spectrometers that have become recently available. These ultra-miniature spectrometers have a very small size as defined by a spectrometer polychromator focal length of ≤40 mm and spectrometer module enclosure sizes of ≤7.5 cm×5 cm×2.5 cm. As the size of a diffraction grating Si-array detector spectrometer module (operating within the 700-1100 nm range) decreases, the spectral background noise from stray scattered light, arising from light scattering inside the spectrometer enclosure, increases and also the spectral resolution decreases. As a result of these latter considerations, it is not obvious that a smaller spectrometer with lower signal/noise and spectral resolution will also be capable of such material identification with good accuracy (i.e. accuracy of greater the 90%).